Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pseudotemporal ordering of single cells reveals metabolic control of postnatal beta cell proliferation

ABSTRACT: Maintenance of blood glucose homeostasis depends on appropriate pancreatic beta cell mass, which is established during early postnatal life through expansion of beta cell numbers. Postnatally, the proliferative capacity of beta cells declines rapidly but the cell extrinsic cues and intracellular signals that cause this decline remain unknown. Here we generated single-cell RNA-seq data of beta cells from multiple postnatal time points and ordered cells based on transcriptional similarity along a linear trajectory. This analysis increased the resolution of transcriptome dynamics during postnatal beta cell development and revealed decreasing mRNA levels of a network of transcription factors, mitochondrial genes and regulators of amino acid metabolism. Through experimental validation we show that these transcription factors and metabolic pathways drive neonatal beta cell proliferation and mass expansion, suggesting a causal role for their regulation in the postnatal decline of beta growth.

ORGANISM(S): Mus musculus

PROVIDER: GSE86479 | GEO | 2017/05/01

SECONDARY ACCESSION(S): PRJNA342036

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

NRF2 Is Required for Neonatal Beta-Cell Growth by Maintaining Redox Balance and Promoting Mitochondrial Biogenesis and Function

Project description:Due to the limited expression of several antioxidant enzymes, β-cells are highly vulnerable to high ROS levels, which can lead to the reduction of functional β-cell mass. During early postnatal ages, both human and rodent β-cells go through a burst of proliferation that quickly declines with age. Here we discovered that the expression of the master antioxidant regulator, Nrf2, is increased during this postnatal burst of β-cell proliferation in humans. Additionally, data from β-cell specific Nrf2 deletion in mice demonstrated that Nrf2 is required for β-cell proliferation, β-cell survival, β-cell identity and β-cell mass expansion at early stages of life. Daily administration of antioxidant NAC to newborn mice showed that Nrf2 mechanism of action strongly relies on maintaining normal redox balance. Interestingly, RNAseq of islets isolated from β-cell specific Nrf2 deleted mice suggests that Nrf2 regulates neonatal β-cell proliferation by promoting mitochondrial ATP synthesis. Our study highlights Nrf2 as an essential transcription factor for maintaining redox balance as well as mitochondrial biogenesis and function to support neonatal β-cell growth and for maintaining functional β-cell mass in adulthood under metabolic stress.

2023-12-19 | GSE242718 | GEO

Juvenile postnatally overfed mice heart microarray anaylsis

Project description:C57BL/6 mice underwent early postnatal overfeeding by litter size reduction (3 pups/dam, instead of 10 pups/dam, in postatally normally fed mice). These overfeeding conditions lead to early and permanent modifications of body weight and to an increase in body fat mass in the adulthood. When these postnatally overfed mice become adult, they develop several cardio-metabolic alterations (mild hypertension, impairment of heart contractility, remodeling, fibrosis, hyperinsulinemia and hyperleptinemia) but also increases in markers of cardiac and plasma oxidative stress. Moreover, we observed a higher sensitivity of the heart to injuries induced by ischemia reperfusion, such as an increase in necrosis. We now aim to establish if these late-coming modifications might be induced in a very early state of postnatal development, such as a postnatal programming situation. To achieve this objective, we are now comparing heart gene expression between 24 days old postnatally overfed and normally fed mice. Comparison of heart gene expression between 24 days old postnatally overfed and normally fed mice.

2013-01-07 | E-GEOD-38995 | biostudies-arrayexpress

Transcription profiling of mouse pancreatic islets on day 14.5 of pregnancy

Project description:The inability of the beta-cell to meet the demand for insulin brought about by insulin resistance leads to type 2 diabetes. In adults, beta-cell replication is one of the mechanisms thought to cause the expansion of beta-cell mass. Efforts to treat diabetes require knowledge of the pathways that drive facultative beta-cell proliferation in vivo. A robust physiological stimulus of beta-cell expansion is pregnancy, and identifying the mechanisms underlying this stimulus may provide therapeutic leads for the treatment of type 2 diabetes. The peak in beta-cell proliferation during pregnancy occurs on day 14.5 of gestation in mice. Using advanced genomic approaches, we globally characterize the gene expression signature of pancreatic islets on day 14.5 of gestation during pregnancy. We identify a total of 1,907 genes as differentially expressed in the islet during pregnancy. We demonstrate that the islet's ability to compensate for relative insulin deficiency during metabolic stress is associated with the induction of both proliferative and survival pathways. A comparison of the genes induced in three different models of islet expansion suggests that diverse mechanisms can be recruited to expand islet mass. The identification of many novel genes involved in islet expansion during pregnancy provides an important resource for diabetes researchers to further investigate how these factors contribute to the maintenance of not only islet mass, but ultimately beta-cell mass.

2010-06-26 | E-MTAB-120 | biostudies-arrayexpress

The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice

Project description:AIMS/HYPOTHESIS: Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function. METHODS: Rkip1 (also known as Pebp1) knockout (Rkip1 (-/-)) mice were characterised in terms of pancreatic and glucose homeostasis, including morphological and functional analysis. Glucose tolerance and insulin sensitivity were examined, followed by assessment of glucose-induced insulin secretion in isolated islets and beta cell mass quantification through morphometry. Further characterisation included determination of endocrine and exocrine proliferation, apoptosis, MAPK activation and whole genome gene expression assays. Capacity to reverse a diabetic phenotype was assessed in adult Rkip1 (-/-) mice after streptozotocin treatment. RESULTS: Rkip1 (-/-) mice exhibit a moderately larger pancreas and increased beta cell mass and pancreatic insulin content, which correlate with an overall improvement in whole body glucose tolerance. This phenotype is established in young postnatal stages and involves enhanced cellular proliferation without significant alterations in cell death. Importantly, adult Rkip1 (-/-) mice exhibit rapid reversal of streptozotocin-induced diabetes compared with control mice. CONCLUSIONS/INTERPRETATION: These data implicate RKIP1 in the regulation of pancreatic growth and beta cell expansion, thus revealing RKIP1 as a potential pharmacological target to promote beta cell regeneration. Pancreatic gene expression of Rkip-1 (Raf kinase inhibitor 1) knockout (KO) and wild type (WT) mice, including three biological replicates in each group.

2012-11-19 | E-GEOD-31150 | biostudies-arrayexpress

Project description:beta-Arrestin-1 is Required for Adaptive beta-Cell Mass Expansion During Obesity

| PRJNA578926 | ENA

Early Peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass

Project description:The progression towards type 2 diabetes depends on the success of the allostatic response of the pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physio and pathological states such as pregnancy, obesity or ageing. The mechanisms, mediating beta cell mass expansion in these scenarios are not well defined. We have recently showed that beta cell mass failed to expand in ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Here we investigate PPAR gamma dependent transcriptional responses occurring during early stages of the adaptation of beta cells to insulin resistance. As it could be expected we have identified genes known to regulate proliferation and survival signals of the beta cells. Moreover we have also identified new pathways induced in ob/ob islets that fail to do so in POKO islets. Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with activation of immune response and is missing in POKO islets. Other PPARγ dependent differentially regulated pathways include cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation. In this study, we used gene expression arrays to investigate differences between four experimental classes by pairs

2012-01-16 | E-GEOD-33647 | biostudies-arrayexpress

Rattus norvegicus

Project description:COUP-TFII Controls Mouse Postnatal Pancreatic β-Cell Mass through GLP-1 β-Catenin

| PRJNA143305 | ENA

Ezh2 maintains proliferation, transcriptional integrity, and the timing of late differentiation during mouse retina development

Project description:We investigated the gene expression profile changes after Ezh2 conditional knockout in the mouse retina at E16.5. Loss of Ezh2 leads to up-regulation of PRC2 targeted genes including cell cycle regulators and multiple genes which are not normally expressed in the retina, including many Hox genes. Loss of Ezh2 resulted in a dramatic decline in progenitor proliferation by postnatal day 3, such that there is an early end to neurogenesis, and disruption of laminar organization. Although there are only minor effects on embryonic retinal development, there is accelerated differentiation of several late born cell types postnatally, including photoreceptors and Mueller glia, which become reactive by postnatal day 14. Peripheral retina was dissected at E16.5 from Pax6alpha-Cre:Ezh2fl/+ and Pax6alpha-Cre:Ezh2fl/null mouse embryos. Total RNA was purified and RNA deep sequencing was done using 4 controls and 4 conditional knockout samples.

2015-07-14 | E-GEOD-65082 | biostudies-arrayexpress

Ezh2 maintains proliferation, transcriptional integrity, and the timing of late differentiation during mouse retina development

2015-07-14 | GSE65082 | GEO

Nkx6.1 regulates islet beta-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors

Project description:Loss of functional beta-cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor Nkx6.1 in rat pancreatic islets induces beta-cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates beta-cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated beta-cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in beta-cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c, resulting in degradation of the cell cycle inhibitor p21CIP1. These studies identify a new bipartite pathway for activation of beta-cell proliferation, suggesting several new targets for expansion of functional beta-cell mass. We set up a microarray using primary rat islets that were left untreated or transduced with adenoviruses overexpressing betagal or Nkx6.1 for 48 h.

2014-02-18 | E-GEOD-55077 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data